Despite the strong association between obesity and hypertension little is known about the mechanism. Since part of the confusion as to the mechanisms of obesity hypertension may be due to complications of long standing hypertension, we have directed our investigative efforts into studying the pathogenesis of hypertension in obese adolescents, a population that represents an early stage of the disease. Based on these studies we will postulate that the hypertension of obesity is primarily related to increased sodium retention by the kidney. We speculate that the combined effects of increased sympathetic nervous system activity, hyperinsulinemia and hyperaldosteronism cause the kidney not only to retain sodium but also to readapt to a new and elevated blood volume and pressure. The following experiments will test this hypothesis: 1) Since our preliminary data suggests that obese adolescents are sodium-sensitive with regards to blood pressure, we will assess the role of sodium intake on blood pressure before and after weight loss. We speculate that weight loss will decrease the degree of sodium-sensitivity of pressure. This change in sodium-sensitivity also will be accompanied by an adaptation of the kidney permitting readjustment to a lower blood volume and cardiac output. Our previous demonstration of increased red cell cotransport activity after weight loss suggest it may be a marker of a change in renal tubular transport capacity. We will now correlate red cell cotransport activity with renal tubular transport capacity before and after weight loss. 2) We will determine if, in obesity, a hyperinsulinemic state marked by resistance to the effects of insulin on glucose metabolism, that the sodium-retaining function of insulin is maintained intact. 3) Since we have documented that obese adolescents have an increased plasma aldosterone and with weight loss the decrease in pressure correlates with the decrease in aldosterone, we will now evaluate the control of aldosterone secretion by measuring urinary excretion of aldosterone and its metabolities (an index of aldosterone secretion) and by measuring adrenal responsiveness to angiotensin II, using Captopril to block the production of angiotensin II. 4) The role of the sympathetic nervous system will be evaluated by measuring plasma catecholamines at rest and during euglycemic hyperinsulinemia and by measuring norepinephrine release, clearance and vascular reactivity.